Dual ATM and DNA-PK inhibitors for use in anti-tumor therapy

Abstract

Provided herein are compounds of the Formula (I), (II), and (III): as well as pharmaceutically acceptable salts thereof, wherein the substituents are those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of oncologic diseases.

What is claimed is: 
     
       1. A compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, tautomer thereof or a mixture thereof; 
         or a pharmaceutically acceptable salt thereof; 
         wherein 
         m is 0, 1, 2, 3, or 4; 
         n is 1, 2, 3, or 4; 
         p and q are each independently 0, 1, 2, or 3; 
       
       
         
           
           
               
               
           
         
       
       is a fused cyclyl, a fused heterocyclyl, a fused aryl or a fused heteroaryl; 
       
         
           
           
               
               
           
         
       
       is a mono-cyclic or bi-cyclic ring, a mono-heterocyclic or bi-heterocyclic ring, an aryl or heteroaryl;
 Y is —(C(R 1a )H—, —C(O)—, —O—, —N(R 5 )—, —S(O) r — (where r is 0, 1 or 2), —S(O) t (NR 5 )— (where t is 1 or 2), —P(O)(R 3 )—O—, —O—P(O)(R 3 )—, P(O)(R 3 )—N(R 5 )—, —N(R 5 )—P(O)(R 3 )—, —CHF—, —CF 2 —, —OC(O)—, —C(O)O—, —C(O)N(R 5 )— or —N(R 5 )C(O)—, 
 M is O, S, or NR 5 ; 
 U is hydrogen or alkyl; 
 V, W, and X are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, optionally substituted haloalkyl, optionally substituted haloalkenyl, optionally substituted haloalkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —R 6 —CN, —R 6 —NO 2 , —R 6 —OR 5 , —R 6 —N(R 4 )R 5 , —O—R 6 —N(R 4 )R 5 , —N═C(R 4 )R 5 , —S(O) r R 4 , —OS(O) 2 CF 3 , —R 6 —C(O)R 4 , —C(S)R 4 , —R 6 —C(O)OR 4 , —C(S)OR 4 , —R 6 —C(O)N(R 4 )R 5 , —C(S)N(R 4 )R 5 , —N(R 5 )C(O)R 4 , —N(R 5 )C(S)R 4 , —N(R 5 )C(O)OR 4 , —N(R 5 )C(S)OR 4 , —N(R 5 )C(O)N(R 4 )R 5 , —N(R 5 )C(S)N(R 4 )R 5 , —N(R 5 )S(O) t R 4 , —N(R 5 )S(O) t N(R 4 )R 5 , —R 6 —S(O) t N(R 4 )R 5 , —O—P(O)(R 4 )R 5 , —O—P(O)R 4 O(R 4 ), —O—P(O)R 4 N(R 4 )R 5 , —N(R 5 )—P(O)(R 4 )R 5 , —N(R 5 )—P(O)R 4 O(R 4 ), —N(R 5 )—P(O)R 4 N(R 4 )R 5 , —N(R 5 )—P(O)O(R 4 )N(R 4 )R 5 , —N(R 5 )—P(O)N(R 4 )R 5 N(R 4 )R 5 , —N(R 5 )C(═NR 5 )R 4 , —N(R 5 )C(═NR 5 )N(R 4 )R 5 , and —N(R 5 )C(═N—CN)N(R 4 )R 5 , wherein each r is independently 0, 1, or 2 and each t is independently 1 or 2; 
 or two adjacent V, or W, or X together with the carbon ring atoms to which they are directly attached, form a fused ring selected from optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; 
 Z is C(R 1a ) or N; 
 R 1a  is a hydrogen, optionally substituted alkyl, halo, CN, NO 2 , or —OR 5 ; 
 R 3  is an optionally substituted alkyl, —OR 5 , or —N(R 4 )R 5 ; 
 each R 4  and R 5  is independently selected from group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted haloalkyl, optionally substituted alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl; 
 or when R 4  and R 5  are each attached to the same nitrogen atom, R 4  and R 5 , together with the nitrogen atom to which they are attached, form a optionally substituted heterocyclyl or optionally substituted heteroaryl; and 
 each R 6  is a direct bond or a linear or branched optionally substituted alkylene chain, a linear or branched optionally substituted alkenylene chain, a linear or branched optionally substituted alkynylene chain, or optionally substituted heterocyclylene. 
 
     
     
       2. The compound according to  claim 1 , wherein Y is —(C(R 1a )H)—, —O—, —N(R 5 )—, —CHF—, or —CF 2 —. 
     
     
       3. The compound according to  claim 1 , wherein Y is —(C(R 1a )H)—. 
     
     
       4. The compound according to  claim 1 , wherein M is O. 
     
     
       5. The compound according to  claim 1 , wherein R 1a  is a hydrogen, alkyl, halo, CN, or —OR 5 . 
     
     
       6. The compound according to  claim 1 , wherein:
 V, W, and X are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, halo, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —R 6 —N(R 4 )R 5 , —O—R 6 —N(R 4 )R 5 , —N(R 5 )S(O) t R 4 , and —N(R 5 )S(O) t N(R 4 )R 5 , wherein each r is independently 0, 1, or 2, and each t is independently 1 or 2; 
 or two adjacent V, or W, or X together with the carbon ring atoms to which they are directly attached, form a fused ring selected from optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl. 
 
     
     
       7. The compound according to  claim 1 , wherein
 V, W, and X are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, halo, optionally substituted heterocyclyl, —R 6 —N(R 4 )R 5 , —O—R 6 —N(R 4 )R 5 , —N(R 5 )S(O) t R 4 , and —N(R 5 )S(O) t N(R 4 )R 5 , wherein each r is independently 0, 1, or 2 and each t is independently 1 or 2; 
 or two adjacent V, or W, or X together with the carbon ring atoms to which they are directly attached, form a fused ring selected from optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, and optionally substituted heteroaryl. 
 
     
     
       8. A compound of Formula (II): 
       
         
           
           
               
               
           
         
         or a stereoisomer, enantiomer, tautomer thereof or a mixture thereof; 
         wherein 
         m is 0, 1, 2, 3, or 4; 
         n is 1, 2, 3, or 4; 
         p is 0, 1, 2, 3; 
       
       
         
           
           
               
               
           
         
       
       is a fused cyclyl, a fused heterocyclyl, a fused aryl or a fused heteroaryl;
 Y is —(C(R 1a )H)—; 
 M is O; 
 U is hydrogen or alkyl; 
 V is selected from the group consisting of nitro, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, optionally substituted haloalkyl, optionally substituted haloalkenyl, optionally substituted haloalkoxy, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —R 6 —CN, —R 6 —NO 2 , —R 6 —OR 5 , —R 6 —N(R 4 )R 5 , —N═C(R 4 )R 5 , —S(O) r R 4  (where r is 0, 1 or 2), —OS(O) 2 CF 3 , —R 6 —C(O)R 4 , —C(S)R 4 , —C(R 4 ) 2 C(O)R 5 , —R 6 —C(O)OR 4 , —C(S)OR 4 , —R 6 —C(O)N(R 4 )R 5 , —C(S)N(R 4 )R 5 , —N(R 5 )C(O)R 4 , —N(R 5 )C(S)R 4 , —N(R 5 )C(O)OR 4 , —N(R 5 )C(S)OR 4 , —N(R 5 )C(O)N(R 4 )R 5 , —N(R 5 )C(S)N(R 4 )R 5 , —N(R 5 )S(O) t R 4 , —N(R 5 )S(O) t N(R 4 )R 5 , —R 6 —S(O) t N(R 4 )R 5 , —N(R 5 )C(═NR 5 )N(R 4 )R 5 , and —N(R 5 )C(═N—CN)N(R 4 )R 5 , wherein each r is independently 0, 1, or 2 and each t is independently 1 or 2; 
 Z is C(R 1a ), or N; 
 R 1a  is a hydrogen, alkyl, halo, CN, NO 2  or —OR 5 ; 
 R 3  is an alkyl, —OR 5 , or —N(R 4 )R 5 ; 
 S is halo, boronate, or boronic acid. 
 
     
     
       9. The compound according to  claim 1 , wherein the compound is selected from the group consisting of:
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopentane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)cyclopropanesulfonamide; 
 3-(1-Cyanoethyl)-N-(2-(3-(dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(4-methylpiperazin-1-yl)pyridin-3-yl)benzenesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(pyrrolidin-1-yl)propoxy)pyridin-3-yl)cyclopropanesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)benzenesulfonamide hydrochloride; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)pyrrolidine-1-sulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-1-methyl-1H-pyrazole-4-sulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)thiophene-3-sulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-4-methoxybenzenesulfonamide hydrochloride; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-4-methylbenzenesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-2-fluorobenzenesulfonamide; 
 N-(2-(4-(Dimethylamino)piperidin-1-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)cyclopropanesulfonamide; 
 3,5-Dichloro-N-(2-(3-(dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide; 
 4-Chloro-N-(2-(3-(dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide hydrochloride; 
 8′-{6-[3-(Dimethylamino)propoxy]-5-[(dimethylsulfamoyl)amino]pyridine-3-yl}-3′-methyl-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinoline]-2′-one hydrochloride; 
 N-(2-([1,4′-Bipiperidin]-1′-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)benzenesulfonamide hydrochloride; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide hydrochloride; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)azetidine-1-sulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-2-fluorobenzenesulfonamide hydrochloride; 
 N-(2-(4-(Dimethylamino)piperidin-1-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)cyclopropanesulfonamide hydrochloride; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)methanesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)cyclopropanesulfonamide; 
 2-Fluoro-N-(5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)benzenesulfonamide hydrochloride; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)thiazole-5-sulfonamide hydrochloride; 
 4-Methyl-N-(5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)piperazine-1-sulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(piperidin-1-yl)propoxy)pyridin-3-yl)piperazine-1-sulfonamide; 
 N-(2-([1,4′-Bipiperidin]-1′-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-2-fluorobenzenesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)oxetane-3-sulfonamide; 
 N-(2-([1,4′-Bipiperidin]-1′-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-2,4-difluorobenzenesulfonamide hydrochloride; 
 N-(2-([1,4′-Bipiperidin]-1′-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)cyclopropanesulfonamide hydrochloride; 
 8′-(6-{[1,4′-Bipiperidine]-1′-yl}-5-[(dimethylsulfamoyl)amino]pyridin-3-yl)-3′-methyl-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinoline]-2′-one; 
 8′-(6-{[1,4′-Bipiperidine]-1′-yl}-5-{[ethyl(methyl)sulfamoyl]amino}pyridin-3-yl)-3′-methyl-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinoline]-2′-one; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(9′-fluoro-3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-4-methylbenzenesulfonamide; 
 N-(2-([1,4′-Bipiperidin]-1′-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclopropane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-6-methylpyridine-3-sulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)-4-hydroxybenzenesulfonamide hydrochloride; 
 N-(2-(4-(Dimethylamino)piperidin-1-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)methanesulfonamide; 
 8′-{6-[4-(Dimethylamino)piperidin-1-yl]-5-[(dimethylsulfamoyl)amino]pyridin-3-yl}-3′-methyl-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinoline]-2′-one; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(4-methylpiperazin-1-yl)pyridin-3-yl)cyclopropanesulfonamide hydrochloride; 
 N-(2-([1,4′-Bipiperidin]-1′-yl)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)methanesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(4-methylpiperazin-1-yl)pyridin-3-yl)methanesulfonamide; 
 8′-{5-[(Dimethylsulfamoyl)amino]-6-(4-methylpiperazin-1-yl)pyridin-3-yl}-3′-methyl-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinoline]-2′-one; 
 N-(2-(3-(Methyl(2,2,2-trifluoroethyl)amino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)methanesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(pyrrolidin-1-yl)propoxy)pyridin-3-yl)benzenesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(pyrrolidin-1-yl)propoxy)pyridin-3-yl)cyclopropanesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(pyrrolidin-1-yl)propoxy)pyridin-3-yl)methanesulfonamide; 
 N-(2-(3-(Dimethylamino)propoxy)-5-(3′-methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)pyridin-3-yl)ethanesulfonamide; 
 N-(5-(3′-Methyl-2′-oxo-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-8′-yl)-2-(3-(methylamino)propoxy)pyridin-3-yl)methanesulfonamide formate; and 
 8′-{5-[(Dimethylsulfamoyl)amino]-6-[3-(pyrrolidin-1-yl)propoxy]pyridin-3-yl}-3′-methyl-2′,3′-dihydrospiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinoline]-2′-one. 
 
     
     
       10. The compound according to  claim 8 , wherein said intermediate is selected from the group consisting of
 8′-Bromo-3′-methylspiro[cyclopentane-1,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 
 8′-Bromo-3′-methylspiro[cyclohexane-1,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 
 8′-Bromo-3′-methyl-2,3,5,6-tetrahydrospiro[pyran-4,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 
 8′-Bromo-3′-methyl-3-((tetrahydro-2H-pyran-2-yl)oxy)spiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 
 8′-Bromo-3′-methylspiro[oxetane-3,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 
 8′-Bromo-9′-fluoro-3′-methylspiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; 
 8′-Bromo-7′-fluoro-3′-methylspiro[cyclobutane-1,1′-pyrrolo[2,3-c]quinolin]-2′(3′H)-one; and 
 8′-Bromo-3′-methylspiro[cyclopropane-1,1′-pyrrolo[2,3-c] quinolin]-2′(3′H)-one. 
 
     
     
       11. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient. 
     
     
       12. A method of treating an oncology disease or disorder, comprising administering a therapeutically effective amount of the compound according to  claim 1  or a pharmaceutically acceptable salt thereof to a patient in need thereof. 
     
     
       13. A method of treating a disease or disorder, comprising administering a therapeutically effective amount of the compound according to  claim 1  or a pharmaceutically acceptable salt thereof to a patient in need thereof. 
     
     
       14. A method of treating an oncology disease or disorder, comprising administering a therapeutically effective amount of compound according to  claim 1  or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the patient is receiving radiotherapy. 
     
     
       15. The method according to  claim 14 , wherein the compound is administered to the patient concomitantly with the radiotherapy. 
     
     
       16. The method according to  claim 14 , wherein the compound is administered to the patient before radiotherapy. 
     
     
       17. The method according to  claim 14 , wherein the compound is administered to the patient after radiotherapy. 
     
     
       18. The method according to  claim 14 , wherein the radiotherapy comprises external, internal, brachytherapy, or systemic exposure. 
     
     
       19. A method of treating an oncology disease or disorder, comprising the step of administering a therapeutically effective amount of the compound according to  claim 1  or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the patient is receiving an anti-tumor agent. 
     
     
       20. The method according to  claim 19 , wherein the anti-tumor agent is cisplatin, oxaliplatin, carboplatin, valrubicin, idarubicin, calicheamicin, or a PARP inhibitor. 
     
     
       21. The method according to  claim 19 , wherein the anti-tumor agent is an anti-tumor biological agent or immunotherapy. 
     
     
       22. The method according to  claim 19 , wherein the compound is administered to the patient concomitantly with the anti-tumor agent. 
     
     
       23. The method according to  claim 19 , wherein the compound is administered to the patient before the anti-tumor agent. 
     
     
       24. The method according to  claim 19 , wherein the compound is administered to the patient after the anti-tumor agent. 
     
     
       25. A method of treatment for warm blooded animals in need of such treatment that involves the administration of the compound according to  claim 1  or a pharmaceutically acceptable salt thereof in a therapeutically effective amount.